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  • 101.
    Malgoyre, A
    et al.
    Institut de Recherche Biomdicale de Armes, La Tronche, France.
    Sanchez, H
    Institut de Recherche Biomdicale de Armes, La Tronche, France.
    Tonini, J
    Institut de Recherche Biomdicale de Armes, La Tronche, France.
    Serrurier, B
    Institut de Recherche Biomdicale de Armes, La Tronche, France.
    Prola, A
    Institut de Recherche Biomdicale de Armes, La Tronche, France.
    Chaillou, Thomas
    Institut de Recherche Biomdicale de Armes, La Tronche, France.
    Simler, N
    Institut de Recherche Biomdicale de Armes, La Tronche, France.
    Bigard, X
    Institut de Recherche Biomdicale de Armes, La Tronche, France.
    Aerobic performance improvment and mitochondrial adaptations after endurance training in hypoxia2011Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 202, nr Suppl. 685Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: The aim of the present study was to examine the effects of hypoxic endurance training on both aerobic performance and mitochondrial changes within plantaris muscle, independently of hematopoietic modifications.

    Methods: Four groups of female rats were constituted either sedentary (S) or trained (T), in either hypoxia (H) or normoxia (N). H conditions corresponded to 14% O2 and the training program to 5 running sessions/week for 5 weeks. Duration and intensity reached progressively 75Õ up to 80% of individual maximal aerobic running velocity (MAV) in either H or N. Performances of each rat were analysed through MAV values and time to exhaustion at 65% MAV (T65). Mitochondrial oxidative capacities (Vmax) for pyruvate (pyr), palmitoyl-carnitine (PC) and palmitoyl-CoA (PCoA) were measured in plantaris skinned fibers. Citrate synthase (CS) and HAD activities were also measured.

    Results: MAV increased in both TN and TH rats (respectively +52%, +39%, P<0.001) without difference between H and N, whereas hypoxia specifically increased T65 (+ 39%, P<0.05) independently of training effect. The training-induced increase in CS activity (P<0.001) was more marked in TN than in TH group (+39% vs +26%, P<0.001) whereas HAD activity rose similarly in TN and TH (respectively +83%, +64%, P<0.05). Physical training increased Vmaxpyr only in N rats (+30%, P<0.001), while VmaxPCoA decreased in hypoxia (P<0.05) without change in VmaxPC. This suggests that LCFA transport by CPT-1 was limiting in hypoxia. As expected, training improved creatine kinase efficiency in N rats (+80%, P<0.005), but no change was shown in H rats.

    Conclusion: Regarding the modest changes in mitochondrial function, it is likely that other factors contribute to explain the improvement of physical performance after an endurance training in hypoxia.

  • 102.
    Marsell, Richard
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Jonsson, Kenneth B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    The phosphate regulating hormone fibroblast growth factor-232010Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 200, nr 2, s. 97-106Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Over the last decade, the regulation of phosphate (Pi) homeostasis has been under intense investigation. By utilizing modern biochemical and genetic tools, the pathophysiological mechanisms behind several known hereditary and acquired hypo- and hyperphosphatemic diseases have been clarified. The results of these efforts have opened new insights into the causes of Pi dysregulation and hereby also the physiological mechanisms determining Pi homeostasis. Although several potential Pi-regulating proteins have been discovered and investigated, current data strongly argues for fibroblast growth factor-23 (FGF23), a hormonal factor produced in bone, as a particularly important regulator of Pi homeostasis. In this article, we review the discovery of the FGF23 protein, as well as its biochemistry, localization of production, receptor specificity and mechanisms of action.

  • 103. Martinka, P
    et al.
    Lai, E Y
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Fähling, M
    Jankowski, V
    Jankowski, J
    Schubert, R
    Gaestel, M
    Persson, A E G
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Persson, P B
    Patzak, A
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Adenosine increases calcium sensitivity via receptor-independent activation of the p38/MK2 pathway in mesenteric arteries2008Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 193, nr 1, s. 37-46Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM: Adenosine (Ado) restores desensitized angiotensin II-induced contractions in the renal arterioles via an intracellular, receptor-independent mechanisms including the p38 mitogen-activated protein kinase (MAPK). In the present study we test the hypothesis that MAPK-activated protein kinase 2 (MK2) mediates the Ado effect downstream from p38 MAPK resulting in an increased phosphorylation of the regulatory unit of the myosin light chain (MLC(20)). METHODS AND RESULTS: Contraction experiments were performed in rings of mesenteric arteries under isometric conditions in C57BL6 and MK2 knock out mice (MK2-/-). Ado pretreatment (10(-5) mol L(-1)) strongly increased Ang II sensitivity, calcium sensitivity and the phosphorylation of MLC(20). Treatment with Ado (3 x 10(-6) or 10(-5) mol L(-1) in between successive Ang II applications) enhanced the desensitized Ang II responses (second to fifth application). Ca(2+) transients were not effected by Ado. Further, blockade of type 1 and type 2 Ado receptors during treatment did not influence the effect. Type 3 receptor activation by inosine instead of Ado had no effect. Conversely, inhibition of nitrobenzylthioinosine-sensitive Ado transporters prevented the effects of Ado. Inhibition of p38 MAPK as well as use of MK2-/- mice prevented contractile Ado effects on the mesenteric arteries and the phosphorylation of MLC(20). CONCLUSION: The study shows that Ado activates the p38 MAPK/MK2 pathway in vascular smooth muscle via an intracellular action, which results in an increased MLC(20) phosphorylation in concert with increased calcium sensitivity of the contractile apparatus. This mechanism can significantly contribute to the regulation of vascular tone, e.g. under post-ischaemic conditions.

  • 104. Mascher, H
    et al.
    Andersson, Helena M
    Örebro universitet, Hälsoakademin.
    Nilsson, P-A
    Ekblom, B
    Blomstrand, E
    Changes in signalling pathways regulating protein synthesis in human muscle in the recovery period after endurance exercise2007Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 191, nr 1, s. 67-75Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM: Exercise induced alterations in the rate of muscle protein synthesis may be related to activity changes in signalling pathways involved in protein synthesis. The aim of the present study was to investigate whether such changes in enzyme phosphorylation occur after endurance exercise. METHODS: Six male subjects performed ergometer cycling exercise for 1 h at 75% of the maximal oxygen uptake. Muscle biopsy samples from the vastus lateralis were taken before, immediately after, 30 min, 1 h, 2 h and 3 h after exercise for the determination of protein kinase B (PKB/Akt), mammalian target of rapamycin (mTOR), glycogen synthase 3 kinase (GSK-3), p70S6 kinase (p70(S6k)) and eukaryotic elongation factor 2 (eEF2) phosphorylation. RESULTS: The phosphorylation of Akt was unchanged directly after exercise, but two- to fourfold increased 1 and 2 h after the exercise, whereas GSK-3alpha and beta phosphorylation were two- to fourfold elevated throughout most of the 3-h recovery period. Phosphorylation of mTOR was elevated threefold directly after, 30 min and 2 h after exercise and eEF2 phosphorylation was decreased by 35-75% from 30 min to 3 h-recovery. Exercise led to a five- to eightfold increase in Ser(424)/Thr(421) phosphorylation of p70(S6k) up to 30 min after exercise, but no change in Thr(389) phosphorylation. CONCLUSIONS: The marked decrease in eEF2 phosphorylation suggests an activation of translation elongation and possibly protein synthesis in the recovery period after sustained endurance exercise. The lack of p70(S6k) activation suggests that translation initiation is activated via alternative pathways, possibly via the activation of eukaryotic initiating factor 2B.

  • 105.
    Mascher, Henrik
    et al.
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap, Eva Blomstrands forskningsgrupp.
    Andersson, H
    Nilsson, P-A
    Ekblom, Björn
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap, Björn Ekbloms forskningsgrupp.
    Blomstrand, Eva
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap, Eva Blomstrands forskningsgrupp.
    Changes in signalling pathways regulating protein synthesis in human muscle in the recovery period after endurance exercise.2007Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 191, nr 1, s. 67-75Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM: Exercise induced alterations in the rate of muscle protein synthesis may be related to activity changes in signalling pathways involved in protein synthesis. The aim of the present study was to investigate whether such changes in enzyme phosphorylation occur after endurance exercise. METHODS: Six male subjects performed ergometer cycling exercise for 1 h at 75% of the maximal oxygen uptake. Muscle biopsy samples from the vastus lateralis were taken before, immediately after, 30 min, 1 h, 2 h and 3 h after exercise for the determination of protein kinase B (PKB/Akt), mammalian target of rapamycin (mTOR), glycogen synthase 3 kinase (GSK-3), p70S6 kinase (p70(S6k)) and eukaryotic elongation factor 2 (eEF2) phosphorylation. RESULTS: The phosphorylation of Akt was unchanged directly after exercise, but two- to fourfold increased 1 and 2 h after the exercise, whereas GSK-3alpha and beta phosphorylation were two- to fourfold elevated throughout most of the 3-h recovery period. Phosphorylation of mTOR was elevated threefold directly after, 30 min and 2 h after exercise and eEF2 phosphorylation was decreased by 35-75% from 30 min to 3 h-recovery. Exercise led to a five- to eightfold increase in Ser(424)/Thr(421) phosphorylation of p70(S6k) up to 30 min after exercise, but no change in Thr(389) phosphorylation. CONCLUSIONS: The marked decrease in eEF2 phosphorylation suggests an activation of translation elongation and possibly protein synthesis in the recovery period after sustained endurance exercise. The lack of p70(S6k) activation suggests that translation initiation is activated via alternative pathways, possibly via the activation of eukaryotic initiating factor 2B.

  • 106.
    Mascher, Henrik
    et al.
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap, Eva Blomstrands forskningsgrupp.
    Ekblom, Björn
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap, Björn Ekbloms forskningsgrupp.
    Rooyackers, Olav
    Blomstrand, Eva
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap, Eva Blomstrands forskningsgrupp.
    Enhanced rates of muscle protein synthesis and elevated mTOR signalling following endurance exercise in human subjects.2011Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 202, nr 2, s. 175-84Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM: The major aim of this study was to determine the fractional rate of protein synthesis (FSR) during the early period of recovery after intensive aerobic exercise in the absence of nutritional supplementation.

    METHODS: Sixteen male subjects performed one-legged cycling exercise for 1 h at approx. 65-70% of their one-legged maximal oxygen uptake. Using the stable isotope technique, the FSR in the vastus lateralis of both legs were determined during two periods, 0-90 min (n = 8) and 90-180 min (n = 8) after exercise. Biopsies were taken from both exercising and resting muscle before exercise, immediately after and following 90 or 180 min of recovery.

    RESULTS: During the initial 90 min of recovery, FSR in the exercising muscle tended to be higher than in the resting muscle (1.57 ± 0.12 vs. 1.44 ± 0.07% 24 h(-1); P = 0.1) and was significantly higher during the period 90-180 min after exercise (1.74 ± 0.14 vs. 1.43 ± 0.12% 24 h(-1) ; P < 0.05). Exercise induced a 60% increase (P < 0.05) in phosphorylation of mTOR and a fivefold increase (P < 0.05) in Thr(389) phosphorylation of p70S6 kinase as well as a 30% reduction (P < 0.05) in phosphorylation of eEF2. Phosphorylation of AMP-activated protein kinase was enhanced by 40% (P < 0.05) after exercise, but no significant effect on phosphorylation of Akt, or eIF2Bε was observed immediately after exercise.

    CONCLUSION: These findings indicate that during the first 3 h of recovery after intensive endurance exercise FSR gradually increases. Moreover, a stimulation of the mTOR-signalling pathway may be at least partially responsible for this elevated protein synthesis.

  • 107. Meehan, CF
    et al.
    Moldovan, M
    Marklund, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Graffmo, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Nielsen, JB
    Hultborn, H
    Intrinsic properties of lumbar motor neurones in the adult G127insTGGG superoxide dismutase-1 mutant mouse in vivo: evidence for increased persistent inward currents2010Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 200, nr 4, s. 361-376Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We demonstrated that, in vivo, at resting membrane potential, spinal motor neurones of the adult G127X mice do not show an increased excitability. However, when depolarized they show evidence of an increased PIC and less SFA which may contribute to excitotoxicity of these neurones as the disease progresses.

  • 108.
    Melville, J. M.
    et al.
    Uppsala University, Sweden.
    Palm, Fredrik
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Uppsala University, Sweden.
    Hultstrom, M.
    Uppsala University, Sweden.
    Editorial Material: Renal oxygenation during haemorrhage is not aggravated by angiotensin II AT1-receptor blockade in ACTA PHYSIOLOGICA, vol 216, issue 2, pp 153-1552016Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 216, nr 2, s. 153-155Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    n/a

  • 109.
    Melville, Jacqueline M.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Palm, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Linkoping Univ, Dept Med & Hlth Sci, S-58183 Linkoping, Sweden..
    Hultström, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Angiotensin II AT1-receptor blockade using Losartan does not impair renal oxygenation following hemorrhage2015Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 215, s. 58-58Artikkel i tidsskrift (Annet vitenskapelig)
  • 110.
    Melville, Jaqueline M
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Palm, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Hultström, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Renal oxygenation during haemorrhage is not aggravated by angiotensin II AT1-receptor blockade2016Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 216, nr 2, s. 153-155Artikkel i tidsskrift (Fagfellevurdert)
  • 111. Mikami, T
    et al.
    Ito, K
    Diaz, Hetzel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Mochiki, E
    Takemi, S
    Tanaka, T
    Tsuda, S
    Jogahara, T
    Sakata, I
    Sakai, T
    Study of termination of postprandial gastric contractions in humans, dogs and Suncus murinus: role of motilin- and ghrelin-induced strong contraction.2018Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 222, nr 2, artikkel-id e12933Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM: Stomach contractions show two types of specific patterns in many species, that is migrating motor contraction (MMC) and postprandial contractions (PPCs), in the fasting and fed states respectively. We found gastric PPCs terminated with migrating strong contractions in humans, dogs and suncus. In this study, we reveal the detailed characteristics and physiological implications of these strong contractions of PPC.

    METHODS: Human, suncus and canine gastric contractions were recorded with a motility-monitoring ingestible capsule and a strain-gauge force transducer. The response of motilin and ghrelin and its receptor antagonist on the contractions were studied by using free-moving suncus.

    RESULTS: Strong gastric contractions were observed at the end of a PPC in human, dog and suncus models, and we tentatively designated this contraction to be a postprandial giant contraction (PPGC). In the suncus, the PPGC showed the same property as those of a phase III contraction of MMC (PIII-MMC) in the duration, motility index and response to motilin or ghrelin antagonist administration. Ghrelin antagonist administration in the latter half of the PPC (LH-PPC) attenuated gastric contraction prolonged the duration of occurrence of PPGC, as found in PII-MMC.

    CONCLUSION: It is thought that the first half of the PPC changed to PII-MMC and then terminated with PIII-MMC, suggesting that PPC consists of a digestive phase (the first half of the PPC) and a discharge phase (LH-PPC) and that LH-PPC is coincident with MMC. In this study, we propose a new approach for the understanding of postprandial contractions.

  • 112.
    Mozibur, Rahman
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Zhu, Di
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Lindblad, Charlotte
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Johansson, Inga-Maj
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Holmberg, Elinor
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Isaksson, Monica
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Wang, Ming-De
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    GABA-site antagonism and pentobarbital actions do not depend on the α-subunit type in the recombinant rat GABA-A receptor2006Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 187, nr 4, s. 479-488Artikkel i tidsskrift (Fagfellevurdert)
  • 113.
    Nevéus, Tryggve
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Sillén, U
    Paediatric Urology Unit, Queen Silvia’s Children’s Hospital, Göteborg, Sweden.
    Lower urinary tract function in childhood; normal development and common functional disturbances2013Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 207, nr 1, s. 85-92Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    This review aims to provide researchers and clinicians involved with the adult lower urinary tract with background knowledge regarding the early development of bladder function and its most common disturbances in childhood. Bladder development begins in weeks 4-6 and the detrusor muscle is formed during weeks 9-12 of gestation. Higher CNS centres are involved in micturition at birth, and the infant usually wakes up, at least briefly, to void. Voiding during the first years of life is often incomplete, owing to detrusor-sphincter dyscoordination, but this disappears when bladder control is attained. Approximately 5-10% of 7-year-old children suffer from daytime incontinence and/or nocturnal enuresis, and a few per cent of them will not outgrow it. Daytime incontinence in childhood is usually attributable to detrusor overactivity, although it is unclear to what extent it is the detrusor or the micturition reflex per se that is overactive. Enuresis - nocturnal incontinence - is caused by either nocturnal polyuria and/or nocturnal detrusor overactivity, in both cases combined with high arousal thresholds. Bladder problems in childhood constitute a risk factor for the development or persistence of bladder problems in adulthood.

  • 114. Niiranen, L.
    et al.
    Makela, K.
    Thalmann, Olaf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Saarela, S.
    Herzig, K-H
    Metabolic regulatory mechanisms in overwintering raccoon dogs (Nyctereutes procyonoides)2014Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 211, nr S696, s. 64-64, artikkel-id P3Artikkel i tidsskrift (Annet vitenskapelig)
  • 115.
    Nikpour, Maryam
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Gustafsson, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Vågesjö, Evelina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Seignez, Cedric
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Giraud, Antoine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Phillipson, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Welsh, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Shb deficiency in endothelium but not in leukocytes is responsible for impaired vascular performance during hindlimb ischemia.2015Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 214, nr 2, s. 200-209Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: Myeloid cells have been suggested to participate in angiogenesis and regulation of vascular function. Shb-deficient mice display both vascular and myeloid cell abnormalities with possible consequences for recovery after hindlimb ischemia. This study was conducted in order to assess the contribution of Shb-deficiency in myeloid cells to impaired vascular function in ischemia. Methods: Wild type and Shb-deficient mice were subjected to peritoneal VEGFA followed by intraperitoneal lavage, after which blood and peritoneal cells were stained for myeloid markers. VEGFA-induced leukocyte recruitment to cremaster muscle was investigated using intravital microscopy of both mouse strains. Blood flow after femoral artery ligation was determined on chimeric mice after bone marrow transplantation. Results: No differences in neutrophil numbers or cell surface phenotypes were detected. Moreover, neutrophil extravasation in VEGFA-activated cremaster muscle was unaffected by Shb deficiency. However, blood and peritoneal CXCR4+ monocytes/macrophages were reduced in response to intraperitoneal VEGFA but not LPS in the absence of Shb. Furthermore, the macrophage population in ischemic muscle was unaffected by Shb-deficiency after two days but reduced seven days after injury. The bone marrow transplantation experiments revealed that mice with wild type vasculature showed better blood flow than those with Shb-deficient vasculature irrespective of leukocyte genotype. Conclusion: The observed aberrations in myeloid cell properties in Shb-deficient mice are likely consequences of an abnormal vascular compartment and are not responsible for reduced muscle blood flow. Structural vascular abnormalities seem to be the primary cause of poor vascular performance under provoked vascular stress in this genetic model.

    Fulltekst (pdf)
    nikpour et al, 2015
  • 116.
    Nilsson, Kristofer F.
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Grishina, V. A.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Glaumann, C.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Gustafsson, L. E.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm.
    Estimation of endogenous adenosine activity at adenosine receptors in guinea-pig ileum using a new pharmacological method2010Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 199, nr 2, s. 231-241Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM: Adenosine modulates neurotransmission and in the intestine adenosine is continuously released both from nerves and from smooth muscle. The main effect is modulation of contractile activity by inhibition of neurotransmitter release and by direct smooth muscle relaxation. Estimation of adenosine concentration at the receptors is difficult due to metabolic inactivation. We hypothesized that endogenous adenosine concentrations can be calculated by using adenosine receptor antagonist and agonist and dose ratio (DR) equations.

    METHODS: Plexus-containing guinea-pig ileum longitudinal smooth muscle preparations were made to contract intermittently by electrical field stimulation in organ baths. Schild plot regressions were constructed with 2-chloroadenosine (agonist) and 8-(p-sulfophenyl)theophylline (8-PST; antagonist). In separate experiments the reversing or enhancing effect of 8-PST and the inhibiting effect of 2-chloroadenosine (CADO) were analysed in the absence or presence of an adenosine uptake inhibitor (dilazep), and nucleoside overflow was measured by HPLC.

    RESULTS: Using the obtained DR, baseline adenosine concentration was calculated to 28 nm expressed as CADO activity, which increased dose dependently after addition of 10(-6) m dilazep to 150 nm (P < 0.05). HPLC measurements yielded a lower fractional increment (80%) in adenosine during dilazep, than found in the pharmacological determination (440%).

    CONCLUSION: Endogenous adenosine is an important modulator of intestinal neuro-effector activity, operating in the linear part of the dose-response curve. Other adenosine-like agonists might contribute to neuromodulation and the derived formulas can be used to calculate endogenous agonist activity, which is markedly affected by nucleoside uptake inhibition. The method described should be suitable for other endogenous signalling molecules in many biological systems.

  • 117.
    Nilsson, Manja
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Fredén, Filip
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Wiklund, P.
    Hambraeus-Jonzon, K.
    No effect of metabolic acidosis on nitric oxide production in hypoxic and hyperoxic lung regions in pigs2011Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 202, nr 1, s. 59-68Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: In the severely ill intensive care patients metabolic acidosis and hypoxia often co-exist. We studied the effects of metabolic acidosis on nitric oxide synthase (NOS) dependent and NOS independent nitric oxide (NO) production in hypoxic and hyperoxic lung (HL) regions in a pig model. Methods: Eighteen healthy anaesthetized pigs were separately ventilated with hypoxic gas to the left lower lobe (LLL) and hyperoxic gas to the rest of the lung. Six pigs received HCl infusion (HCl group), six pigs received the non-specific NOS inhibitor N omega-nitro-l-arginine methyl ester (l-NAME) and HCl infusions (l-NAME + HCl group) and six pigs received buffered Ringer's solution (control group). NO concentration in exhaled air (ENO), NOS activity in lung tissue, and regional pulmonary blood flow were measured. Results: Metabolic acidosis, induced by infusion of HCl, decreased the relative perfusion to the hypoxic LLL from 7 (3) [mean (SD)] to 3 (1) % in the HCl group (P < 0.01), and from 4 (1) to 1 (1) % in the l-NAME + HCl group (P < 0.05), without any measurable significant changes in ENO from hypoxic or HL regions There were no significant differences between the HCl and control groups for Ca2+-dependent (cNOS) or Ca2+-independent NOS (iNOS) activity in hypoxic or HL regions. Conclusions: Metabolic acidosis augmented the hypoxic pulmonary vasoconstriction, without any changes in pulmonary NOS dependent or NOS independent NO production. When acidosis was induced during ongoing NOS blockade, the perfusion of hypoxic lung regions was almost abolished, indicating acidosis-induced pulmonary vasoconstriction was not NO dependent.

  • 118.
    Nylander, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    The impact of cyclooxygenase inhibition on duodenal motility and mucosal alkaline secretion in anaesthetized rats2011Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 201, nr 1, s. 179-192Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Aim: Non-steroidal anti-inflammatory drugs (NSAIDs) are effective in the treatment of various human diseases. However, these drugs also have serious adverse effects in the gastrointestinal tract. In the duodenum NSAIDs inhibit mucosal alkaline secretion (DMAS), an important protective mechanism against the acid emptied from the stomach in most species, including humans. Surprisingly, NSAIDs have been shown to stimulate DMAS in an anaesthetized rat model. The aim of this review was to summarize the effects of NSAIDs and selective cyclooxygenase-2 (COX-2) inhibition on duodenal function in the rat and provide an explanation for why these drugs stimulate DMAS. Included are new data examining the effect of alpha-adrenergic drugs on duodenal motility and DMAS. Methods: Experiments were performed in anaesthetized rats. The proximal duodenum was perfused luminally with an isotonic NaCl solution. DMAS, motility, fluid flux and epithelial permeability were assessed in the absence and presence of various COX inhibitors. Results: COX inhibition induced duodenal motility, increased DMAS and augmented the sensitivity as well as the maximal response of the duodenal mucosa to lidocaine- or hypotonicity-induced increases in mucosal permeability. Furthermore, the ability of the duodenum to absorb water and to adjust osmolality in response to luminal hypotonicity was improved in COX-inhibited animals. These improvements are mediated predominately via inhibition of COX-2. Conclusions: Inhibition of COX-2 in rats with postoperative duodenal ileus induces muscle contractions, which in turn activate a nicotinic receptor-dependent intramural reflex that stimulates duodenocytes to increase the activity of apical Cl-/HCO3- exchangers, resulting in a rise in DMAS.

  • 119.
    Nylander, Olof
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    Pihl, Liselotte
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    Luminal hypotonicity increases duodenal mucosal permeability by a mechanism involving 5-hydroxytryptamine2006Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 186, nr 1, s. 45-58Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: To investigate whether 5-HT participates in the mediation of the hypotonicity-induced increase in duodenal mucosal permeability.

    Methods: Proximal duodenum in anesthetized rats was perfused in situ with a hypotonic NaCl solution and effects on duodenal motility, net fluid flux, mucosal permeability (blood-to-lumen clearance of 51Cr-EDTA) and the release of 5-HT into the luminal solution studied in the presence of the cyclooxygenase inhibitor indomethacin.

    Results: Perfusion of the duodenum with 50 mM NaCl increased mucosal permeability eightfold, increased the luminal output of 5-HT twofold and induced net fluid absorption. This rise in permeability was enhanced 25% by 5-HT (3 · 10-3 M), reduced by the 5-HT3-receptor antagonists granisetron (10-4 - 3 · 10-4 M) or ondansetron (10-5 - 10-4 M) or by the 5-HT4 receptor antagonist SB 203186 (10-4 M). The 5-HT3/4 receptor antagonist tropisetron, at 10-4 M, did not affect while 3 · 10-4 and 3 · 10-3 M augmented the hypotonicity-induced increase in mucosal permeability. Lidocaine (1.1 · 10-3 M) similarly potentiated while tetrodotoxin (5 · 10-5 M) inhibited the hypotonicity-induced increase in mucosal permeability. Compared to animals treated with indomethacin alone ondansetron and granisetron augmented (by 30-40%) while tropisetron and lidocaine reduced (by 60-70%) the hypotonicity-induced net fluid absorption. TTX and all 5-HT receptor antagonists, except tropisetron, depressed duodenal motility.

    Conclusions: Luminal hypotonicity increases duodenal mucosal permeability by a neural mechanism involving 5-HT acting on 5-HT3 and 5-HT4 receptors. 5-HT also appears to participate in the regulation of the hypotonicity-induced fluid flux.

  • 120.
    Nylander, Olof
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    Sjöblom, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    Modulation of mucosal permeability by vasoactive intestinal peptide or lidocaine affects the adjustment of luminal hypotonicity in rat duodenum2007Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 189, nr 4, s. 325-335Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims: To examine whether modulation of paracellular solute permeability affects the capability of the duodenum to adjust luminal osmolality.

    Methods: Proximal duodenum was perfused with a hypotonic NaCl solution and effects on paracellular permeability to 51Cr-EDTA, motility, anion secretion, net fluid flux and perfusate osmolality determined in anaesthetized rats in the absence and presence of the COX-2 inhibitor parecoxib. Vasoactive intestinal peptide (VIP) was used to reduce and lidocaine to augment the hypotonicity-induced increase in paracellular permeability.

    Results: Luminal hypotonicity slightly increased paracellular permeability in control animals. Parecoxib induced motility, increased electrolyte and fluid secretion, potentiated the hypotonicity-induced rise in paracellular permeability and enhanced the capability to adjust luminal osmolality. VIP, given to control animals stimulated electrolyte and fluid secretion and augmented the capability to adjust luminal osmolality. Administration of VIP to parecoxib-treated animals increased secretion further, markedly reduced the hypotonicity-induced increase in permeability but did not change the osmolality-adjusting capability. Luminal lidocaine potentiated the hypotonicity-induced increase in permeability, reduced the hypotonicity-induced net fluid absorption and the osmolality-adjusting capability was 50% greater than in controls. Lidocaine, given to parecoxib-treated animals potentiated the hypotonicity-induced increase in permeability, reduced the hypotonicity-induced net fluid absorption but did not change the osmolality-adjusting capability.

    Conclusions: Vasoactive intestinal peptide reduces the osmolality-adjusting capacity of the duodenum by inhibiting paracellular solute permeability but improves this capacity by stimulating active electrolyte and fluid secretion. In contrast, lidocaine improves the osmolality-adjusting capability by augmenting paracellular solute transport but depresses it by reducing the hypotonicity-induced net fluid absorption.

  • 121.
    Palm, Fredrik
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Hälsouniversitetet. Uppsala University, Sweden.
    Editorial Material: ET-1 increases reactive oxygen species in hypoxic glomeruli during high salt intake in ACTA PHYSIOLOGICA, vol 213, issue 3, pp 559-5602015Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 213, nr 3, s. 559-560Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    n/a

  • 122.
    Palm, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    ET-1 increases reactive oxygen species in hypoxic glomeruli during high salt intake2015Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 213, nr 3, s. 559-560Artikkel i tidsskrift (Annet vitenskapelig)
  • 123.
    Pantazis, Antonios
    et al.
    Linkoping Univ, Linkoping, Sweden..
    Kaneko, Maki
    Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA..
    Westerlund, Annie M.
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Biofysik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Delemotte, Lucie
    KTH, Skolan för teknikvetenskap (SCI), Tillämpad fysik, Biofysik. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Saitta, Sulagna
    Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA..
    Olcese, Riccardo
    Univ Calif Los Angeles, Los Angeles, CA USA..
    Multiscale biophysical investigation of a novel KCNA2 (KV1.2) variant associated with epilepsy2019Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 227, s. 64-64Artikkel i tidsskrift (Annet vitenskapelig)
  • 124. Patinha, D.
    et al.
    O'Neil, J.
    Franzen, S.
    Pihl, L.
    Palm, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Renal oxygen metabolism in animals feed a low salt diet2014Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 211, nr S696, s. 80-80, artikkel-id P33Artikkel i tidsskrift (Annet vitenskapelig)
  • 125.
    Pelsers, M. M. A. L.
    et al.
    Department of Movement Sciences, Maastricht University, Maastricht, Netherlands & Department of Movement Sciences, Maastricht University, Maastricht, Netherlands.
    Tsintzas, K.
    Institute of Clinical Research, University of Nottingham Medical School, Nottingham, United Kingdom.
    Boon, Hanneke
    Department of Human Biology, Maastricht University, Maastricht, Netherlands.
    Jewell, K.
    Institute of Clinical Research, University of Nottingham Medical School, Nottingham, United Kingdom.
    Norton, L.
    Institute of Clinical Research, University of Nottingham Medical School, Nottingham, United Kingdom.
    Luiken, J. J. F. P.
    Department of Molecular Genetics, Maastricht University, Maastricht, Netherlands.
    Glatz, J. F. C.
    Department of Molecular Genetics, Maastricht University, Maastricht, Netherlands.
    van Loon, L. J.
    Department of Movement Sciences, Maastricht University, Maastricht, the Netherlands & Department of Human Biology, Maastricht University, Maastricht, Netherlands.
    Skeletal muscle fatty acid transporter protein expression in type 2 diabetes patients compared with overweight, sedentary men and age-matched, endurance-trained cyclists2007Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 190, nr 3, s. 209-219Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM: Membrane fatty acid transporters can modulate the balance between fatty acid uptake and subsequent storage and/or oxidation in muscle tissue. As such, skeletal muscle fatty acid transporter protein expression could play an important role in the etiology of insulin resistance and/or type 2 diabetes.

    METHODS: In the present study, fatty acid translocase (FAT/CD36), plasma membrane-bound fatty acid-binding protein (FABPpm) and fatty acid transport protein 1 (FATP1) mRNA and protein expression were assessed in muscle tissue obtained from 10 sedentary, overweight type 2 diabetes patients (60 +/- 2 years), 10 sedentary, weight-matched normoglycemic controls (60 +/- 2 years) and 10 age-matched, endurance trained cyclists (57 +/- 1 years).

    RESULTS: Both FAT/CD36 and FATP1 mRNA and protein expression did not differ between groups. In contrast, FABPpm mRNA and protein expression were approx. 30-40% higher in the trained men compared with the diabetes patients (P < 0.01) and sedentary controls (P < 0.05).

    CONCLUSIONS: Skeletal muscle FAT/CD36, FABPpm and FATP1 mRNA and protein expression are not up- or downregulated in a sedentary and/or insulin resistant state. In contrast, FABPpm expression is upregulated in the endurance trained state and likely instrumental to allow greater fatty acid oxidation rates. © 2007 The Authors.

  • 126. Perlewitz, A.
    et al.
    Persson, A. Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Patzak, A.
    The juxtaglomerular apparatus2012Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 205, nr 1, s. 6-8Artikkel i tidsskrift (Fagfellevurdert)
  • 127.
    Persson, A. E. G.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Carlstrom, M.
    Renal purinergic signalling in health and disease2015Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 213, nr 4, s. 805-807Artikkel i tidsskrift (Annet vitenskapelig)
  • 128.
    Persson, P.
    et al.
    Uppsala University, Sweden.
    Friederich-Persson, M.
    Uppsala University, Sweden.
    Fasching, A.
    Uppsala University, Sweden.
    Hansell, P.
    Uppsala University, Sweden.
    Inagi, R.
    University of Tokyo, Japan.
    Palm, Fredrik
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Uppsala University, Sweden.
    Adenosine A(2)a receptor stimulation prevents proteinuria in diabetic rats by promoting an anti-inflammatory phenotype without affecting oxidative stress2015Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 214, nr 3, s. 311-318Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AimDiabetic patients are at increased risk for kidney disease. There is presently no clinical treatment available that effectively protects kidney function in diabetics. This study investigates whether chronic stimulation of the adenosine A(2a) receptor (A(2a)AR) protects kidney function in insulinopenic diabetic rats. MethodsStreptozotocin-induced diabetic rats and corresponding controls were chronically treated with the adenosine A(2a)AR agonist CGS21680 throughout the four-week diabetes duration. Kidney function was thereafter investigated, and urine and plasma samples were collected for analysis of protein, oxidative stress and inflammatory markers. ResultsGlomerular filtration rate, renal blood flow, filtration fraction and diabetes-induced kidney hypoxia were all unaffected by chronic A(2a)AR stimulation. Furthermore, diabetic rats had increased oxidative stress, which was further increased by chronic A(2a)AR stimulation. However, the 10-fold increased urinary protein excretion observed in the diabetic rats was completely prevented by chronic A(2a)AR stimulation. These beneficial effects were accompanied by reduced levels of the pro-inflammatory TNF- and increased levels of the anti-inflammatory IL-10 as well as decreased infiltration of macrophages, glomerular damage and basement membrane thickness. ConclusionChronic A(2a)AR stimulation prevents proteinuria and glomerular damage in experimental diabetes via an anti-inflammatory mechanism independent of oxidative stress and kidney hypoxia.

  • 129.
    Persson, Patrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Fasching, Angelica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Palm, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Acute intrarenal angiotensin (1-7) infusion decreases diabetes-induced glomerular hyperfiltration but increases kidney oxygen consumption in the rat2019Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 226, nr 1, artikkel-id e13254Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: Common kidney alterations early after the onset of insulinopenic diabetes include glomerular hyperfiltration, increased oxygen consumption and tissue hypoxia. Increased activity of the renin-angiotensin-aldosterone system (RAAS) has been implicated in most of these early alterations. The RAAS peptide angiotensin (1-7) has the potential to modulate RAAS-mediated alterations in kidney function. Thus, the aim of the present study was to determine the acute effects of angiotensin (1-7) in the kidney of insulinopenic type 1 diabetic rat and the results compared to that of normoglycaemic controls.

    Methods: Renal haemodynamics and oxygen homeostasis were measured 3 weeks after administration of streptozotocin before and after acute intrarenal infusion of angiotensin (1-7) at a dose of 400 ng min(-1).

    Results: Arterial pressure and renal blood flow were similar between groups and not affected by exogenous angiotensin (1-7). Diabetics presented with glomerular hyperfiltration, increased urinary sodium excretion and elevated kidney oxygen consumption. Angiotensin (1-7) infusion normalized glomerular filtration, increased urinary sodium excretion, decreased proximal tubular reabsorption, and elevated kidney oxygen consumption even further. The latter resulting in tubular electrolyte transport inefficiency. Angiotensin (1-7) did not affect tissue oxygen tension and had no significant effects in controls on any of the measured parameters.

    Conclusion: Diabetes results in increased responsiveness to elevated levels of angiotensin (1-7) which is manifested as inhibition of tubular sodium transport and normalization of glomerular filtration. Furthermore, elevated angiotensin (1-7) levels increase kidney oxygen consumption in the diabetic kidney even further which affects tubular electrolyte transport efficiency negatively.

  • 130.
    Persson, Patrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Friederich-Persson, Malou
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Fasching, Angelica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Hansell, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Inagi, Reiko
    University of Tokyo Graduate School of Medicine, Tokyo, Japan.
    Palm, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Adenosine A2 a receptor stimulation prevents proteinuria in diabetic rats by promoting an anti-inflammatory phenotype without affecting oxidative stress2015Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 214, nr 3, s. 311-318Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM: Diabetic patients are at increased risk for kidney disease. There is presently no clinical treatment available that effectively protects kidney function in diabetics. The present study investigates if chronic stimulation of the adenosine A2a receptor (A2a AR) protects kidney function in insulinopenic diabetic rats.

    METHODS: Streptozotocin-induced diabetic rats and corresponding controls were chronically treated with the adenosine A2a AR agonist CGS21680 throughout the four-week diabetes duration. Kidney function was thereafter investigated and urine and plasma samples were collected for analysis of protein, oxidative stress and inflammatory markers.

    RESULTS: Glomerular filtration rate, renal blood flow, filtration fraction and diabetes-induced kidney hypoxia were all unaffected by chronic A2a AR stimulation. Furthermore, diabetic rats had increased oxidative stress, which was further increased by chronic A2a AR stimulation. However, the 10-fold increased urinary protein excretion observed in the diabetic rats was completely prevented by chronic A2a AR stimulation. These beneficial effects were accompanied by reduced levels of the pro-inflammatory TNF-α and increased levels of the anti-inflammatory IL-10 as well as decreased infiltration of macrophages, glomerular damage and basement membrane thickness.

    CONCLUSION: Chronic A2a AR stimulation prevents proteinuria and glomerular damage in experimental diabetes via an anti-inflammatory mechanism independent of oxidative stress and kidney hypoxia.

  • 131.
    Persson, Patrik
    et al.
    Uppsala universitet, Integrativ Fysiologi.
    Hansell, Peter
    Uppsala universitet, Integrativ Fysiologi.
    Palm, Fredrik
    Uppsala universitet, Integrativ Fysiologi.
    Tubular reabsorption and diabetes-induced glomerular hyperfiltration2010Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 200, nr 1, s. 3-10Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Elevated glomerular filtration rate (GFR) is a common observation in early diabetes mellitus and closely correlates with the progression of diabetic nephropathy. Hyperfiltration has been explained to be the result of a reduced load of sodium and chloride passing macula densa, secondarily to an increased proximal reabsorption of glucose and sodium by the sodium-glucose co-transporters. This results in an inactivation of the tubuloglomerular feedback (TGF), leading to a reduced afferent arteriolar vasoconstriction and subsequently an increase in GFR. This hypothesis has recently been questioned due to the observation that adenosine A(1)-receptor knockout mice, previously shown to lack a functional TGF mechanism, still display a pronounced hyperfiltration when diabetes is induced. Leyssac demonstrated in the 1960s (Acta Physiol Scand58, 1963:236) that GFR and proximal reabsorption can work independently of each other. Furthermore, by the use of micropuncture technique a reduced hydrostatic pressure in Bowman's space or in the proximal tubule of diabetic rats has been observed. A reduced pressure in Bowman's space will increase the pressure gradient over the filtration barrier and can contribute to the development of diabetic hyperfiltration. When inhibiting proximal reabsorption with a carbonic anhydrase inhibitor, GFR decreases and proximal tubular pressure increases. Measuring intratubular pressure allows a sufficient time resolution to reveal that net filtration pressure decreases before TGF is activated which highlights the importance of intratubular pressure as a regulator of GFR. Taken together, these results imply that the reduced intratubular pressure observed in diabetes might be crucial for the development of glomerular hyperfiltration.

  • 132.
    Persson, Patrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Hansell, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Palm, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Tubular reabsorption and diabetes-induced glomerular hyperfiltration2010Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 200, nr 1, s. 3-10Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Elevated glomerular filtration rate (GFR) is a common observation in early diabetes mellitus and closely correlates with the progression of diabetic nephropathy. Hyperfiltration has been explained to be the result of a reduced load of sodium and chloride passing macula densa, secondarily to an increased proximal reabsorption of glucose and sodium by the sodium-glucose co-transporters. This results in an inactivation of the tubuloglomerular feedback (TGF), leading to a reduced afferent arteriolar vasoconstriction and subsequently an increase in GFR. This hypothesis has recently been questioned due to the observation that adenosine A(1)-receptor knockout mice, previously shown to lack a functional TGF mechanism, still display a pronounced hyperfiltration when diabetes is induced. Leyssac demonstrated in the 1960s (Acta Physiol Scand58, 1963:236) that GFR and proximal reabsorption can work independently of each other. Furthermore, by the use of micropuncture technique a reduced hydrostatic pressure in Bowman's space or in the proximal tubule of diabetic rats has been observed. A reduced pressure in Bowman's space will increase the pressure gradient over the filtration barrier and can contribute to the development of diabetic hyperfiltration. When inhibiting proximal reabsorption with a carbonic anhydrase inhibitor, GFR decreases and proximal tubular pressure increases. Measuring intratubular pressure allows a sufficient time resolution to reveal that net filtration pressure decreases before TGF is activated which highlights the importance of intratubular pressure as a regulator of GFR. Taken together, these results imply that the reduced intratubular pressure observed in diabetes might be crucial for the development of glomerular hyperfiltration.

  • 133.
    Pihl, Liselotte
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    Nylander, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    Products of cyclooxygenase-2 depress duodenal function in rats subjected to abdominal surgery2006Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 186, nr 4, s. 279-90Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: Abdominal surgery evokes powerful biological responses that affect gastrointestinal functions. Here we investigate the role of the COX-1 and COX-2 isoforms in postoperative duodenal ileus.

    Methods: Proximal duodenum of anesthetized rats was perfused in situ with isotonic or hypotonic (50 mM) NaCl. Mucosal bicarbonate secretion, motility, mucosal permeability and effluent osmolality were determined in the absence and presence of different COX inhibitors.

    Results: The majority of control animals had no or few duodenal contractions and bicarbonate secretion averaged 10.9 ± 1.4 µmol · cm-1 · h-1. These “paralytic” controls responded to hypotonic NaCl with a small increase in mucosal permeability. In control animals exhibiting spontaneous duodenal contractions the bicarbonate secretion was 50% higher and the hypotonicity-induced net increase in mucosal permeability 7-fold higher than in “paralytic” controls. Treatment with the selective COX-2 inhibitors rofecoxib or parecoxib induced duodenal motility, increased bicarbonate secretion and potentiated the hypotonicity-induced increase in mucosal permeability. COX-2-inhibited animals had a twofold greater capacity to adjust luminal osmolality than “paralytic” controls. The selective COX-1 inhibitor SC-560 only transiently stimulated motility and bicarbonate secretion and the hypotonicity-induced increase in mucosal permeability was smaller than in COX-2 inhibited animals.

    Conclusions: Abdominal surgery increases the synthesis of prostanoids, particularly via the COX-2 isoform. This compromises the ability of the duodenum to contract and to secrete HCO3- and to adjust luminal osmolality possibly via altered mucosal permeability. It is proposed that studies of gastrointestinal functions in animals subjected to abdominal surgery should include animals pre-treated with a COX-2 inhibitor.

  • 134.
    Pihl, Liselotte
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Sjöblom, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Seidler, U.
    Sedin, John
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Nylander, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Motility-induced but not vasoactive intestinal peptide-induced increase in luminal alkalinization in rat duodenum is dependent on luminal Cl-2010Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 200, nr 2, s. 181-191Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: To investigate whether the motility- and the vasoactive intestinal peptide (VIP)-induced increase in luminal alkalinization in the duodenum is dependent on luminal Cl-. Methods: Experiments were performed in anaesthetized rats in vivo. The proximal duodenum was perfused luminally with an isotonic solution, containing zero or low Cl- and the effects on luminal alkalinization, motility, fluid flux and epithelial permeability were determined. Parecoxib, a COX-2 inhibitor, was used to induce duodenal contractions. Results: Control rats lacked duodenal wall contractions while parecoxib-treated ones exhibited contractions throughout the experiment. Most animals had a net fluid absorption during the perfusion with isotonic NaCl. Luminal alkalinization was about 100% higher in parecoxib-treated rats than in controls. Cl--free solutions did not affect epithelial permeability or motility but decreased luminal alkalinization by >= 50% and decreased net fluid absorption in both control and parecoxib-treated animals. Reduction in luminal Cl- decreased alkalinization in a concentration-dependent manner. The parecoxib-induced increase in alkalinization was markedly reduced in the absence of luminal Cl-. VIP increased luminal alkalinization and induced fluid secretion. The lack of luminal Cl- did not affect the VIP-induced increase in alkalinization but reduced fluid secretion. Conclusions: The parecoxib-induced increase in luminal alkalinization is highly dependent on luminal Cl- and it is proposed that COX-2 inhibition, via induction of duodenal motility, enhances HCO3- efflux through stimulation of apical Cl-/HCO3- exchange in duodenal epithelial cells. Although the VIP-induced stimulation of fluid secretion is partly dependent on luminal Cl-, the VIP-induced increase in luminal alkalinization is not.

  • 135.
    Pihl, Liselotte
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    Wilander, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Nylander, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    Comparative study of the effect of luminal hypotonicity on mucosal permeability in rat upper gastrointestinal tract2008Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 193, nr 1, s. 67-78Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: To investigate whether the increase in mucosal permeability in the duodenum, induced by luminal hypotonicity, also occurs in the stomach and the jejunum and whether this increase in permeability can be explained by epithelial injury. Methods: The stomach, duodenum or jejunum of the anaesthetized rat were perfused with a hypotonic solution and effects on mucosal permeability (blood-to-lumen clearance of radioactive probes); luminal alkalinization and net fluid flux were determined in the absence and presence of cyclooxygenase inhibition. Results: The hypotonicity-induced (50 mM NaCl) increase in duodenal mucosal permeability was markedly larger in cyclooxygenase-2-inhibited animals than in controls and associated with a 20% decrease in luminal alkalinization and increased fluid absorption. Perfusion with 50 mM NaCl increased duodenal mucosal permeability to all probes investigated, i.e. C-14-urea, C-14-methyl-D-glucose, Cr-51-EDTA and C-14-inulin. The percentage increase in permeability was the greatest for inulin and the lowest for urea. Luminal hypotonicity caused superficial villous tip damage in some but not in all duodenal specimens but there was no difference in morphology between controls and cyclooxygenase-2-inhibited animals. Jejunum, but not the stomach, responded to luminal hypotonicity by increasing net fluid absorption, mucosal permeability (greater than sixfold) and the rate of luminal alkalinization (> 100%). Conclusions: The stomach does not respond while the jejunum is more sensitive to hypotonicity-induced increase in mucosal permeability than the duodenum. The hypotonicity-induced increase in duodenal mucosal permeability most probably constitutes a physiological mechanism that entails widening of paracellular pathways, which facilitates the transport of osmolytes into the lumen.

  • 136.
    Porra, Liisa
    et al.
    Univ Helsinki, Dept Phys, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Helsinki, Finland..
    Albu, Gergely
    Univ Hosp Geneva, Anaesthesiol Invest Unit, Geneva, Switzerland..
    Broche, Ludovic
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala Univ, Amiens Univ Hosp, Dept Pediat Intens Care, Hedenstierna,Lab Dept Surg Sci, Uppsala, Sweden..
    Degrugilliers, Loic
    Amiens Univ Hosp, Dept Pediat Intens Care, Amiens, France..
    Wallin, Matts
    Maquet Crit Care AB, Solna, Sweden..
    Halback, Magnus
    Maquet Crit Care AB, Solna, Sweden..
    Petak, Ferenc
    Univ Szeged, Dept Med Phys & Informat, Szeged, Hungary..
    Habre, Walid
    Univ Hosp Geneva, Anaesthesiol Invest Unit, Geneva, Switzerland..
    Bayat, Sam
    Univ Hosp Geneva, Anaesthesiol Invest Unit, Geneva, Switzerland..
    Imaging dynamic lung strain and specific elastance by K-edge subtraction computed tomography2016Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 217, s. 137-137Artikkel i tidsskrift (Fagfellevurdert)
  • 137. Režen, T.
    et al.
    Kovanda, A.
    Eiken, Ola
    KTH, Skolan för teknik och hälsa (STH), Naturvetenskap och biomedicin, Omgivningsfysiologi. KTH, Skolan för teknik och hälsa (STH), Centra, Centrum för flyg- och rymdfysiologi, SAPC.
    Mekjavic, I.B.
    Rogelj, B.
    Expression changes in human skeletal muscle miRNAs following 10 days of bed rest in young healthy males2014Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 210, nr 3, s. 655-666Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: Studies in humans show global changes in mRNA and protein expression occur in human skeletal muscle during bed rest. As microRNAs are important regulators of expression, we analysed the global microRNA expression changes in human muscle following 10 days of sustained bed rest, with the rationale that miRNAs play key roles in atrophy of skeletal muscle. Methods: We analysed expression of miRNA and selected target proteins before and after 10 days of bed rest in biopsies obtained from the vastus lateralis muscle of 6 healthy males. Results: Fifteen of 152 miRNAs detected in human muscle tissue were differentially expressed, and all of them with exception of two were downregulated. The downregulated miRNAs include the following: miR-206, a myomir involved in function and maintenance of skeletal muscle; miR-23a, involved in insulin response and atrophy defence; and several members of the let-7 family involved in cell cycle, cell differentiation and glucose homeostasis. Predicted gene targets of these miRNAs are members of the MAPK, TNF receptor, ALK1, TGF-beta receptor and SMAD signalling pathways. All of these pathways were previously indicated to be involved in skeletal muscle response to physical inactivity. We also measured protein expression of selected miRNA targets and observed a decrease in HDAC4. Conclusion: Our data demonstrate that miRNAs in postural muscles are affected by sustained inactivity and unloading, as induced by prolonged bed rest, and hence are potentially involved in regulation of skeletal muscle adjustments to inactivity. We also propose new miRNAs involved in regulation of biological processes in adult human muscle.

  • 138. Režen, T.
    et al.
    Kovanda, A.
    Eiken, Ola
    KTH, Skolan för teknik och hälsa (STH), Naturvetenskap och biomedicin, Omgivningsfysiologi.
    Mekjavič, I.
    Rogelj, B.
    Response to the letter to the editor by Kristensen MM, Helge JW and Dela F2015Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 215, nr 2, s. 76-78Artikkel i tidsskrift (Fagfellevurdert)
  • 139.
    Rune, A.
    et al.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Salehzadeh, F.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Szekeres, F.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Kuhn, I.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Osler, M. E.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Al-Khalili, L.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Evidence against a sexual dimorphism in glucose and fatty acid metabolism in skeletal muscle cultures from age-matched men and post-menopausal women2009Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 197, nr 3, s. 207-215Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: In vivo whole body differences in glucose/lipid metabolism exist between men and women. Thus, we tested the hypothesis that intrinsic sex differences exist in skeletal muscle gene expression and glucose/lipid metabolism using cultured myotubes. Methods: Myotube cultures were prepared for gene expression and metabolic studies from vastus lateralis skeletal muscle biopsies obtained from age-matched men (n = 11; 59 +/- 2 years) and post-menopausal women (n = 10; 60 +/- 1 years). Results: mRNA expression of several genes involved in glucose and lipid metabolism was higher in skeletal muscle biopsies from female vs. male donors, but unaltered between the sexes in cultured myotubes. Basal and insulin-stimulated glucose uptake, as well as glucose incorporation into glycogen, was similar in myotube cultures derived from male vs. female donors. In males vs. females, insulin increased glucose uptake (1.3 +/- 0.1 vs. 1.5 +/- 0.1-fold respectively) and incorporation into glycogen (2.3 +/- 0.3 vs. 2.0 +/- 0.3-fold respectively) to the same extent. Basal fatty acid oxidation and rate of uptake/accumulation was similar between sexes. In response to the 5'AMP-activated protein kinase activator AICAR, lipid oxidation was increased to the same extent in myotubes established from male vs. female donors (1.6 +/- 0.6 vs. 2.0 +/- 0.3-fold respectively). Moreover, the AICAR-induced rate of uptake/accumulation was similar between sexes. Conclusion: Differences in metabolic parameters and gene expression profiles between age-matched men and post-menopausal women noted in vivo are not observed in cultured human skeletal muscle cells. Thus, the sexual dimorphism in glucose and lipid metabolism is likely a consequence of systemic whole body factors, rather than intrinsic differences in the skeletal muscle proper.

  • 140.
    Rügheimer, Louise
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Hansell, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Wolgast, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Determination of the charge of the plasma proteins and consequent Donnan equilibrium across the capillary barriers in the rat microvasculature2008Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 194, nr 4, s. 334-339Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim

    Due to the negatively charged proteins in plasma, a Donnan equilibrium will be formed between plasma and interstitium or, as in the glomerulus, between glomerular plasma and Bowman's space. The phenomenon is of great physiological significance in the sense that the electro-osmotic pressure offered by the small ions attracted to the proteins may account for an important part of the total colloid osmotic pressure and also as the electric potential consequent to the Donnan distribution will affect the transcapillary transport of all charged molecular compounds. The present study aimed at estimating the protein charge in rat plasma in order to validate its importance for colloid osmotic pressure and potential.

    Methods

    The charge of the plasma proteins was determined in vitro from the concentration of sodium across a cellophane membrane separating a rat plasma sample from saline alone. However, in order to improve the sensitivity of the method, the studies were carried out at an ionic strength of 1/10 of physiological saline.

    Results

    The average charge of plasma was estimated at 0.23 +/- 0.003 mEq g(-1) protein (mean +/- SE), and the standard variation at +/- 0.01 mEq g(-1), i.e. about 5%. At the normal protein concentration in Wistar rats of 50 g L-1, the charge of the proteins in systemic plasma was calculated to be 11.5 mEq L-1, whereas in glomerular and peritubular capillary plasma, the larger protein concentration increases the protein charge to 14.4 mEq L-1.

    Conclusion

    The results verify that the plasma protein charge accounts for about one-third of the total colloid osmotic pressure and that the obtained potential will constitute a major driving force for the transport of charged molecular compounds.

  • 141.
    Rügheimer, Louise
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi, Integrativ Fysiologi.
    Johnsson, C.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Maric, C.
    Department of Medicine, Georgetown University Medical Centre, Washington, DC, USA.
    Hansell, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Hormonal regulation of renomedullary hyaluronan2008Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 193, nr 2, s. 191-198Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM

    Hyaluronan (HA) is involved in renomedullary water handling through its water-binding capacity. This study addressed the effect of hormones involved in regulating fluid-electrolyte homeostasis on renomedullary HA content in vivo and in vitro.

    METHODS

    The kidneys from rats treated with L-NAME, indomethacin, vasopressin (AVP) or methylprednisolone (MP) during euvolaemia or water loading were analysed for HA by RIA, ELISA and histochemical staining. HA was measured in renomedullary interstitial cells treated with AVP, angiotensin II (Ang II) or a combination of AVP and Ang II.

    RESULTS

     Baseline renal cortical and medullary HA content was unaffected by 2 h of intravenous treatment with L-NAME (NOS inhibitor) or indomethacin (cyclo-oxygenase inhibitor), whereas AVP reduced medullary HA by 33%. During 2 h of acute water loading, diuresis was accompanied by an increase in renomedullary HA (+45%), but cortical HA was unaffected. In both L-NAME- and indomethacin-treated animals, the water loading-induced increase in renomedullary HA was absent, indicating involvement of NO and prostaglandins. After 7 days of MP treatment, medullary HA was reduced by 40%, but the water loading-induced elevation in HA remained. In cultured renomedullary interstitial cells, AVP reduced the HA content in the supernatant by 63%, and simultaneous treatment with Ang II reduced the HA content even further (95%).

    CONCLUSION

     AVP reduces HA content, and NO and prostaglandins are needed for the increase in HA during water loading.

  • 142.
    Saellstroem, J.
    et al.
    Uppsala University, Sweden .
    Eriksson, T.
    Uppsala University, Sweden .
    Fredholm, B. B.
    Karolinska Institute, Sweden .
    Persson, A. E. G.
    Uppsala University, Sweden .
    Palm, Fredrik
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Hälsouniversitetet.
    Inhibition of sodium-linked glucose reabsorption normalizes diabetes-induced glomerular hyperfiltration in conscious adenosine A(1)-receptor deficient mice2014Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 210, nr 2, s. 440-445Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AimGlomerular hyperfiltration is commonly observed in diabetics early after the onset of the disease and predicts the progression of nephropathy. Sustained hyperglycaemia is also closely associated with kidney hypertrophy and increased electrolyte and glucose reabsorption in the proximal tubule. In this study, we investigated the role of the increased tubular sodium/glucose cotransport for diabetes-induced glomerular hyperfiltration. To eliminate any potential confounding effect of the tubuloglomerular feedback (TGF) mechanism, we used adenosine A(1)-receptor deficient (A(1)AR(-/-)) mice known to lack a functional TGF mechanism and compared the results to corresponding wild-type animals (A(1)AR(+/+)). MethodsDiabetes was induced by an intravenous bolus injection of alloxan. Glomerular filtration rate (GFR) was determined in conscious mice by a single bolus injection of inulin. The sodium/glucose cotransporters were inhibited by phlorizin 30min prior to GFR measurements. ResultsNormoglycaemic animals had a similar GFR independent of genotype (A(1)AR(+/+) 23311 vs. A(1)AR(-/-) 241 +/- 25Lmin(-1)), and induction of diabetes resulted in glomerular hyperfiltration in both groups (A(1)AR(+/+) 380 +/- 25 vs. A(1)AR(-/-) 336 +/- 35Lmin(-1); both Pless than0.05). Phlorizin had no effect on GFR in normoglycaemic mice, whereas it reduced GFR in both genotypes during diabetes (A(1)AR(+/+) 365 +/- 18 to 295 +/- 19, A(1)AR(-/-) 354 +/- 38 to 199 +/- 15Lmin(-1); both Pless than0.05). Notably, the reduction was more pronounced in the A(1)AR(-/-) (Pless than0.05). ConclusionThis study demonstrates that increased tubular sodium/glucose reabsorption is important for diabetes-induced hyperfiltration, and that the TGF mechanism is not involved in these alterations, but rather functions to reduce any deviations from a new set-point.

  • 143.
    Sahlin, Kent
    Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap, Åstrandlaboratoriet, Forskningsgruppen Mitokondriell funktion och metabolisk kontroll.
    Mitochondrial function during exercise2016Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 216, nr S707, s. S06-1-Artikkel i tidsskrift (Fagfellevurdert)
  • 144.
    Salah, Heba
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi. Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Fury, W.
    Regeneron Pharmaceut, Tarrytown, NY USA..
    Gromada, J.
    Regeneron Pharmaceut, Tarrytown, NY USA..
    Bai, Y.
    Regeneron Pharmaceut, Tarrytown, NY USA..
    Tchkonia, T.
    Mayo Clin, Coll Med, Robert & Arlene Kogod Ctr Aging, Rochester, MN USA..
    Kirkland, J. L.
    Mayo Clin, Coll Med, Robert & Arlene Kogod Ctr Aging, Rochester, MN USA..
    Larsson, L.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Karolinska Inst, Dept Clin Neurosci, Clin Neurophysiol, Stockholm, Sweden.;Penn State Univ, Dept Biobehav Hlth, State Coll, PA USA..
    Muscle-specific differences in expression and phosphorylation of the Janus kinase 2/Signal Transducer and Activator of Transcription 3 following long-term mechanical ventilation and immobilization in rats2018Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 222, nr 3, artikkel-id e12980Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: Muscle wasting is one of the factors most strongly predicting mortality and morbidity in critically ill intensive care unit (ICU). This muscle wasting affects both limb and respiratory muscles, but the understanding of underlying mechanisms and muscle-specific differences remains incomplete. This study aimed at investigating the temporal expression and phosphorylation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in muscle wasting associated with the ICU condition to characterize the JAK/STAT proteins and the related changes leading or responding to their activation during exposure to the ICU condition.

    Methods: A novel experimental ICU model allowing long-term exposure to the ICU condition, immobilization and mechanical ventilation, was used in this study. Rats were pharmacologically paralysed by post-synaptic neuromuscular blockade and mechanically ventilated for durations varying between 6hours and 14days to study muscle-specific differences in the temporal activation of the JAK/STAT pathway in plantaris, intercostal and diaphragm muscles.

    Results: The JAK2/STAT3 pathway was significantly activated irrespective of muscle, but muscle-specific differences were observed in the temporal activation pattern between plantaris, intercostal and diaphragm muscles.

    Conclusion: The JAK2/STAT3 pathway was differentially activated in plantaris, intercostal and diaphragm muscles in response to the ICU condition. Thus, JAK2/STAT3 inhibitors may provide an attractive pharmacological intervention strategy in immobilized ICU patients, but further experimental studies are required in the study of muscle-specific effects on muscle mass and function in response to both short- and long-term exposure to the ICU condition prior to the translation into clinical research and practice.

  • 145.
    Salari, Sajjad
    et al.
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi.
    Silverå Ejneby, Malin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelning för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Brask, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelning för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Elinder, Fredrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelning för neurobiologi. Linköpings universitet, Medicinska fakulteten.
    Isopimaric acid - a multi-targeting ion channel modulator reducing excitability and arrhythmicity in a spontaneously beating mouse atrial cell line2018Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 222, nr 1, artikkel-id e12895Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AimAtrial fibrillation is the most common persistent cardiac arrhythmia, and it is not well controlled by present drugs. Because some resin acids open voltage-gated potassium channels and reduce neuronal excitability, we explored the effects of the resin acid isopimaric acid (IPA) on action potentials and ion currents in cardiomyocytes. MethodsSpontaneously beating mouse atrial HL-1 cells were investigated with the whole-cell patch-clamp technique. Results1-25 mol L-1 IPA reduced the action potential frequency by up to 50%. The effect of IPA on six different voltage-gated ion channels was investigated; most voltage-dependent parameters of ion channel gating were shifted in the negative direction along the voltage axis, consistent with a hypothesis that a lipophilic and negatively charged compound binds to the lipid membrane close to the positively charged voltage sensor of the ion channels. The major finding was that IPA inactivated sodium channels and L- and T-type calcium channels and activated the rapidly activating potassium channel and the transient outward potassium channel. Computer simulations of IPA effects on all of the ion currents were consistent with a reduced excitability, and they also showed that effects on the Na channel played the largest role to reduce the action potential frequency. Finally, induced arrhythmia in the HL-1 cells was reversed by IPA. ConclusionLow concentrations of IPA reduced the action potential frequency and restored regular firing by altering the voltage dependencies of several voltage-gated ion channels. These findings can form the basis for a new pharmacological strategy to treat atrial fibrillation.

    Fulltekst (pdf)
    fulltext
  • 146.
    Saudi, Wan Salman Wan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    Halim, Abdul
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Webb, Dominic-Luc
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Gillberg, A. L.
    Feldreich, T. Rudholm
    Sundbom, M.
    Karlbom, U.
    Naslund, E.
    Sommansson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Sjöblom, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    Neuropeptide S reduce small intestinal motility in rats and humans2014Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 211, nr S696, s. 94-94, artikkel-id P61Artikkel i tidsskrift (Annet vitenskapelig)
  • 147.
    Schagatay, Erika
    et al.
    Mittuniversitetet, Fakulteten för humanvetenskap, Avdelningen för hälsovetenskap.
    Johansson, Orio
    Lund University.
    Abrahamsson, Erik
    Lund University.
    Diving Response and Lung Capacity of Philippine Sama-Bajau Professional Breath-Hold Divers2017Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 219, nr S710, artikkel-id P-66Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION: Freedivers possess several special physiological features and have been reported to have stronger diving response and larger vital capacity (VC) than non-divers. Several populations in South-East Asia live as marine hunter-gatherers dependent upon daily freediving with little equipment. One group is the Sama-Bajau in Indonesia, Philippines and Malaysia. Our aim was to investigate the diving response and lung physiology of the Sama-Bajau breath-hold diving population in the Phillipines, which has not previously been studied. 

    MATERIALS AND METHODS: Nine male professional breath-hold divers were recruited from a Sama-Bajau diving community near Davao in the Philippines. Their mean(SD) age was 27(3)years, height 166(2)cm, and weight 58(2)kg. Divers made simulated dives by maximal apneas with face immersion in cool water, while heart-rate (HR) was recorded to determine the diving response by the HR reduction. Lung variables were measured using a portable spirometer, and diving time and depth of working dives in the sea were logged.

    RESULTS: Mean(SE) HR-reduction was 39(3)%, at a maximal voluntary apnea of 67(7)s duration. VC was 3.9(0.6)L (96% of predicted for a Malaysian population, NS) and forced expiratory volume in the 1st second/forced VC was 89.6(3.4)% (105% of predicted, P<0.05). Maximal diving depth was 15 m, and mean depth 5(2) m. Diving shifts lasted 2-3h, with approximately 50% of the time spent underwater.

    CONCLUSION: The diving response was more pronounced than in non divers but in the range typical for breath-hold divers. VC was similar to predicted for non-divers but smaller than in e.g. competition divers. FEV1/FVC was slightly higher than in the normal population. We concluded that long term daily "natural" diving to 5-15m does not increase lung volume, but may have some effects on lung function.

  • 148.
    Schagatay, Erika
    et al.
    Mittuniversitetet, Fakulteten för humanvetenskap, Avdelningen för hälsovetenskap.
    Patrician, Alexander
    Mittuniversitetet, Fakulteten för humanvetenskap, Avdelningen för hälsovetenskap.
    Engan, Harald
    LHL Klinikkene Roros, Roros, Norway.
    Lodin-Sundström, Angelica
    Mittuniversitetet, Fakulteten för humanvetenskap, Avdelningen för hälsovetenskap.
    Spleen Contraction and Hb Increase after Nitrate Ingestion may Explain Enhanced Apneic Diving Performance2017Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 219, nr S710, s. 32-32, artikkel-id P-42Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION: Ingesting nitrate-rich beetroot juice (BJ) has been suggested to enhance physical performance by reducing the oxygen cost, which could be useful in apneic diving. We previously found that after ingestion of BJ, arterial oxygen saturation was higher after static apneas (Engan et.al, Resp. Physiol & Neurobiol, 2012) and after dynamic apneas involving exercise (Patrician & Schagatay. Scand.J.Med.Sci.Sports, 2016). Our aim was to investigate the effect of BJ ingestion on spleen contraction and the resulting Hb increase, a mechanism known to prolong apneas (Schagatay et.al, J.Appl.Physiol, 2001).

    MATERIALS AND METHODS: Eight volunteers aged 24±2 years simulated diving by performing maximal apneas with face immersion during prone rest ~2.5h after ingesting 70 ml BJ (5 mmol NO3-) or placebo (0.003 mmol NO3-) on separate days in a weighted order. We measured spleen diameters for volume calculation and capillary Hb before and after "dives".

    RESULTS: Baseline (mean±SE) spleen volume was 269±33 mL with placebo and 206±27 mL after BJ ingestion (P<0.05). Post "dive" spleen volumes were smaller, but similar at 168±35 mL and 193±25 mL, respectively (NS). Baseline Hb was 145.4±3.4 g/L with placebo and 149.8±2.6 g/L with BJ (P<0.05). Post "dive" Hb had increased to 152.0±4.8 g/L with placebo and 153.7±3.0 g/L with BJ (NS). 

    CONCLUSION: With BJ ingestion spleen volume was reduced and Hb elevated even before the "dive". The elevated Hb at the start of apnea would likely have a positive effect on apneic duration by enhancing circulating oxygen stores. The positive effect of nitrate on performance in various sports could in part be due to its spleen-emptying effect, causing a natural blood boosting, which is a novel finding.

  • 149.
    Schiöth, Helgi B.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Nordström, K. J. V.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Fredriksson, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Mining the gene repertoire and ESTs for G protein-coupled receptors with evolutionary perspective2007Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 190, nr 1, s. 21-31Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The purpose of this article was to review recent progress in mining the gene repertoire and expressed sequence tags (ESTs) for the super-family of G protein-coupled receptors (GPCRs) in the form of a proceeding from the Nordic GPCR meeting held at the Nobel Forum, Karolinska Institute in August 2006. We update and give an overview of the expansion of the main families of GPCRs; Glutamate, Rhodopsin, Adhesion, Frizzled and Secretin (GRAFS) in perspective of fully sequenced genomes. We look into the most recent findings including the work that has been carried out on the spotted green puffer fish (Tetraodon nigroviridis), mouse (Mus musculus), chicken (Gallus gallus), slime mold (Dictyostelium discoideum) and the plant pathogenic fungus Magnaporthe grisea. We use examples from our recent work on chicken GPCRs to highlight the importance of detailed assembly and curation of sequences and how that can affect percentage similarity and phylogeny. ESTs can give valuable information about expression patterns. GPCRs have comparatively low numbers of EST suggesting that GPCRs are in generally expressed in lower amount than other genes. We discuss similarities in the evolution of the trace amine associated receptors with other sensory receptors.

  • 150.
    Schrottmaier, Waltraud C.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Institute for Vascular Biology and Thrombosis Research, Medical University of Vienna, Austria.
    Salzmann, M.
    Badrnya, S.
    Morava, S.
    Luik, A-L
    Kral-Pointner, J. B.
    Mussbacher, M.
    Karlsson, M.
    Forsell, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Assinger, A.
    Platelet-stored antibodies potently diminish viral infection in vitro and in vivo2019Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 227, nr S718, s. 187-187Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Besides their primary role in haemostasis, platelets are actively involved in immune responses as they respond to various inflammatory stimuli, including microbial infection. Further, platelets contain intracellular IgG, but their physiologic function remains unknown. Thus, we aimed to elucidate the function of platelet-derived IgGs and their effect on viral infections. Human and murine platelets contained IgG which were released upon shear stress. However, IgG loss did not correlate with P-Selectin exposure or CXCL4 release and α-granule deficient (Nbeal2-/-) platelets failed to show reduced IgG content and release, indicating an extragranular IgG storage site within platelets. While platelet IgG could derive from megakaryocytes that have taken up IgG from the bone marrow microenvironment, naïve platelets also took up IgG directly from plasma in vitro and in vivo. Murine platelets from anti-IAV IgG seropositive mice reduced IAV infection in vitro and in vivo more efficiently than plasma containing comparable IgG levels. Further, human platelets from anti-CMV IgG seropositive but not seronegative donors also potently neutralized in vitro CMV-infection of HUVEC under microvascular shear stress. Our data indicate that IgG storage in platelets may not be restricted to α-granules. Further, our results show that platelets have the potential to mediate potent IgG-mediated antiviral effects both in vitro and in vivo directly at foci of infection. This indicates that platelet-derived IgG may represent a yet unexplored mechanism for focused serological immunity.

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